The overall scope of this project deals with the ontogeny and phylogeny of immunity. Amphibian models are and will continue to be used to unravel problems that are of evolutionary interest as well as those that are not restricted to the phylogenetic position of the experimental animals used. Research concentrates on problems in three areas. I. Evolution of the major histocompatibility complex (MHC): We are interested in MHC polymorphism in frogs and in the very existence of a MHC in salamanders. We are also combining embryonic transplantation protocols, flow cytometry, and in vivo and in vitro assays to determine whether MHC restriction occurs in frogs and whether the thymus plays a role in this restriction. II. Ontogeny of immunity to self and non-self: Immunogenetic and immunobiolobical aspects of allotolerance is being studied throughout larval life in Xenopus. The hypothesis that if an organism fails to encounter a set of self antigens during a critical time during ontogeny, it fails to develop tolerance to these antigens is also being tested in a developmental study involving self eye and pituitary grafts. III. Ontogenetic and phylogenetic studies of lymphocytes: We are investigating neural crest contributions to the thymus, the earliest origins of thymocytes in embryos, and alternative pathways of hematopoiesis in the developing frog. Heterogeneity of adult T and B cells is also being probed with hybridoma reagents, negative and positive selection procedures, and in vivo and in vitro assays of function.